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An anion doped aluminium chlorofluoride AlCl0.1F2.8(OTeF5)0.1 (ACF-teflate) was synthesized. The material contains pentafluoroorthotellurate (teflate) groups, which mimic fluoride ions electronically, but are sterically more demanding. They are embedded into the amorphous structure. The latter was studied by PDF analysis, EXAFS data and MAS NMR spectroscopy. The mesoporous powder is a Lewis superacid, and ATR-IR spectra of adsorbed CD3CN reveal a blue-shift of the adsorption band by 73 cm1, which is larger than the shift for SbF5. Remarkably, ACF-teflate catalyzes dehydrofluorination reactions of monofluoroalkanes to yield olefins in C6D6. In these cases, no Friedel-Crafts products were formed.

A potential role of dietary factors on the risk of ovarian cancer (OVC) has been suggested by ecologic studies due to observed differences in international incidence rates ([1][1]). The contribution of dietary factors to the etiology of OVC has been suggested through the modulation of the endogenous

GES-1 is a class A extended-spectrum β-lactamase conferring resistance to penicillins, narrow- and expanded-spectrum cephalosporins, and ceftazidime. However, GES-1 poorly hydrolyzes aztreonam and cephamycins and exhibits very low k cat values for carbapenems. Twenty-two GES variants have been discovered thus far, differing from each other by 1 to 3 amino acid substitutions that affect substrate specificity. GES-11 possesses a Gly243Ala substitution which seems to confer to this variant an increased activity against aztreonam and ceftazidime. GES-12 differs from GES-11 by a single Thr237Ala substitution, while GES-14 differs from GES-11 by the Gly170Ser mutation, which is known to confer increased carbapenemase activity. GES-11 and GES-12 were kinetically characterized and compared to GES-1 and GES-14. Purified GES-11 and GES-12 showed strong activities against most tested β-lactams, with the exception of temocillin, cefoxitin, and carbapenems. Both variants showed a significantly increased rate of hydrolysis of cefotaxime, ceftazidime, and aztreonam. On the other hand, GES-11 and GES-12 (and GES-14) variants all containing Ala243 exhibited increased susceptibility to classical inhibitors. The crystallographic structures of the GES-11 and GES-14 β-lactamases were solved. The overall structures of GES-11 and GES-14 are similar to that of GES-1. The Gly243Ala substitution caused only subtle local rearrangements, notably in the typical carbapenemase disulfide bond. The active sites of GES-14 and GES-11 are very similar, with the Gly170Ser substitution leading only to the formation of additional hydrogen bonds of the Ser residue with hydrolytic water and the Glu166 residue.

A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.

We report the first description of the metallo-β-lactamase VIM-31, a new variant of VIM-2 with Tyr224His and His252Arg mutations, in Enterobacter cloacae 11236, which was isolated from blood specimens of a patient with colonic adenocarcinoma in Belgium. bla VIM-31 was found on a class 1 integron located on a self-transferable but not typeable 42-kb plasmid. Compared to values published elsewhere for VIM-2, the purified VIM-31 enzyme showed weaker catalytic efficiency against all the tested beta-lactam agents (except for ertapenem), resulting from lower k cat (except for ertapenem) and higher K m values for VIM-31.

The CphAII protein from the hyperthermophile Aquifex aeolicus shows the five conserved motifs of the metallo-β-lactamase (MBL) superfamily and presents 28% identity with the Aeromonas hydrophila subclass B2 CphA MBL. The gene encoding CphAII was amplified by PCR from the A. aeolicus genomic DNA and overexpressed in Escherichia coli using a pLex-based expression system. The recombinant CphAII protein was purified by a combination of heating (to denature E. coli proteins) and two steps of immobilized metal affinity chromatography. The purified enzyme preparation did not exhibit a β-lactamase activity but showed a metal-dependent phosphodiesterase activity versus bis-p-nitrophenyl phosphate and thymidine 5'-monophosphate p-nitrophenyl ester, with an optimum at 85°C. The circular dichroism spectrum was in agreement with the percentage of secondary structures characteristic of the MBL αββα fold.

Background Finite mixture models posit the existence of a latent categorical variable and can be used for probabilistic classification. The authors illustrate the use of mixture models for dietary pattern analysis. An advantage of this approach is taking classification uncertainty into account. Methods Participants were a random sample of women from the European Prospective Investigation into Cancer. Food consumption was measured using dietary questionnaires. Mixture models identified latent classes in food consumption data, which were interpreted as dietary patterns. Results Among various assumptions examined, models allowing the variance of foods to vary within and between classes fit better than alternatives assuming constant variance (the K-means method of cluster analysis also makes the latter assumption). An eight-class model was best fitting and five patterns validated well in a second random sample. Patterns with lower classification uncertainty tended to be better validated. One pattern showed low consumption of foods despite being associated with moderate body mass index. Conclusion Mixture modelling for dietary pattern analysis has advantages over both factor and cluster analysis. In contrast to these other methods, it is easy to estimate pattern prevalence, to describe patterns and to use patterns to predict disease taking classification uncertainty into account. Owing to substantial error in food consumptions, any analysis will usually find some patterns that cannot be well validated. While knowledge of classification uncertainty may aid pattern evaluation, any method will better identify patterns from food consumptions measured with less error. Mixture models may be useful to identify individuals who under-report food consumption.

The metallo-β-lactamase (MBL) GOB-1 was expressed via a T7 expression system in Escherichia coli BL21(DE3). The MBL was purified to homogeneity and shown to exhibit a broad substrate profile, hydrolyzing all the tested β-lactam compounds efficiently. The GOB enzymes are unique among MBLs due to the presence of a glutamine residue at position 116, a zinc-binding residue in all known class B1 and B3 MBL structures. Here we produced and studied the Q116A, Q116N and Q116H mutants. The substrate profiles were similar for each mutant, but with significantly reduced activity compared with that of the wild-type. In contrast to the Q116H enzyme, which bound two zinc ions just like the wild-type, only one zinc ion is present in Q116A and Q116N. These results suggest that the Q116 residue plays a role in the binding of the zinc ion in the QHH site.

OBJECTIVE: To identify combinations of food groups that explain as much variation in absolute intakes of 23 key nutrients and food components as possible within the country-specific populations of the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: The analysis covered single 24-h dietary recalls (24-HDR) from 36,034 subjects (13,025 men and 23,009 women), aged 35-74 years, from all 10 countries participating in the EPIC study. In a set of 39 food groups, reduced rank regression (RRR) was used to identify those combinations (RRR factors) that explain the largest proportion of variation in intake of 23 key nutrients and food components, namely, proteins, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, sugars (sum of mono- and disaccharides), starch, fibre, alcohol, calcium, iron, potassium, phosphorus, magnesium, vitamin D, beta-carotene, retinol and vitamins E, B1, B2, B6, B12 and C (RRR responses). Analyses were performed at the country level and for all countries combined. RESULTS: In the country-specific analyses, the first RRR factor explained a considerable proportion of the total nutrient intake variation in all 10 countries (27.4-37.1%). The subsequent RRR factors were much less important in explaining the variation (

Epidemiological studies conducted thus far have mainly used a single-nutrient approach which may not be sufficient in detecting diet–cancer relationships. The aim of the study was to examine the association of a food pattern based on explained variations in fatty acid intake by means of reduced rank regression with breast cancer risk. Study participants were female subjects (n 15 351) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study free of cancer at baseline and with complete dietary and outcome information followed for an average of 6·0 years. Among those, 137 incident cases of invasive breast cancer were identified. We identified a food pattern characterized by low consumption of bread, and fruit juices, and high consumption of processed meat, fish, butter and other animal fats, and margarine explaining >42 % of total variation in fatty acid intake (SFA, MUFA, n-3 PUFA, n-6 PUFA). Intake of all four fatty acid fractions was positively associated with the pattern score. Adherence to this food pattern adjusted for covariates was associated with a two-fold risk (hazard ratio 2·00; 95 % CI 1·30, 3·09) of breast cancer comparing extreme tertiles of the pattern score. There was no evidence of effect modification by menopausal status, overweight status and use of hormone replacement therapy, respectively. In conclusion, a food pattern characterized by high-fat food choices was significantly associated with increased risk of breast cancer. Given that the food pattern was high in all fatty acid fractions, we found evidence for total dietary fat rather than for specific fatty acids to be associated with breast cancer risk.

BACKGROUND: International multicentre studies on diet and cancer are relatively new in epidemiological research. They offer a series of challenging methodological issues for the evaluation of the association between dietary exposure and disease outcomes, which can both be quite heterogeneous across different geographical regions. This requires considerable work to standardize dietary measurements at the food and the nutrient levels. METHODS: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a calibration study was set up to express individual dietary intakes according to the same reference scale. A linear regression calibration model was used to correct the association between diet and disease for measurement errors in dietary exposures. In the present work, we describe an approach for analysing the EPIC data, using as an example the evaluation of the association between fish intake and colorectal cancer incidence. RESULTS: Sex- and country-specific attenuation factors ranged from 0.083 to 0.784, with values overall higher for men compared with women. Hazard ratio estimates of colorectal cancer for a 10 g/day increase in fish intake were 0.97 [95% confidence interval (CI): 0.95-0.99] and 0.93 (0.88-0.98), before and after calibration, respectively. CONCLUSIONS: In a multicentre study, the diet/disease association can be evaluated by exploiting the whole variability of intake over the entire study. Calibration may reduce between-centre heterogeneity in the diet-disease relationship caused by differential impact of measurement errors across cohorts. Udgivelsesdato: 2008-Apr

For epidemiological studies, a simple semiquantitative FFQ was developed to assess the frequency of intake of food items demonstrated with graphically displayed portion sizes. As a validation study, a random sample of 393 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study completed 2 unannounced 24-h dietary recalls (24HDR) and the FFQ during 1 y. To calculate food and nutrient intakes, we compared the use of fitted portion sizes with the use of predefined portion sizes. Fitted portion sizes were calculated by summing food intakes over the 2 24HDR and dividing the sum by the frequency of intake reported in the FFQ for each FFQ food item, leading to similar mean intakes for FFQ and 24HDR. As predefined portion sizes, amounts that had been used in previous dietary assessments in EPIC-Potsdam were used. Mean intake of 12 food groups was 102% for men or women with fitted portion sizes and 79% for men and 95% for women with predefined portion sizes of intake measured with 2 24HDR. However, deattenuated, energy-adjusted correlation coefficients between FFQ and 24HDR were not better for 19 nutrients by the use of fitted portion sizes, with a mean correlation coefficient of 0.53 for men and 0.56 for women. Mean correlation coefficients for food groups also were similar for fitted and predefined portion sizes. Fitting portion sizes using recent reference data from a random sample of study participants improved the quantitative assessment of food and nutrient intake, but not ranking of study participants, compared with predefining portion sizes based on prior knowledge.

Background and Purpose— Data from prospective studies on the associations between B vitamin plasma levels and the risk of stroke are limited. We investigated the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phophate (PLP) levels on the risk of ischemic stroke and transient ischemic attack (TIA) in a large, prospective German cohort. Methods— Incident cases of ischemic stroke or TIA were identified among 25 770 participants (age 35 to 65 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study during 6.0±1.5 years of follow-up. The present analysis is based on a case-cohort study comprising 779 subjects free from cardiovascular disease and 188 incident cases of cerebral ischemia (ischemic stroke or TIA). Multivariable Cox proportional-hazard models were applied to evaluate the association between B vitamin levels and risk of cerebral ischemia. Results— Participants in the lowest tertile of vitamin B12 values were at increased risk of cerebral ischemia compared with subjects in the highest tertile; this was not observed, however, for either folate or PLP. In subgroup analyses, the relative risks were similar in magnitude for stroke and TIA. When various combinations of B vitamin tertile levels were analyzed, only combined low folate and vitamin B12 levels (relative risk, 2.24; 95% CI, 1.10 to 4.54) were significantly related to an increased risk of cerebrovascular ischemia. Conclusions— Our data suggest that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia. This effect may be mediated at least partly through elevations of homocysteine levels.

OBJECTIVE—We aimed to develop a precise risk score for the screening of large populations for individuals at high risk of developing type 2 diabetes based on noninvasive measurements of major risk factors in German study populations. RESEARCH DESIGN AND METHODS—A prospective cohort study (European Prospective Investigation into Cancer and Nutrition [EPIC]-Potsdam study) of 9,729 men and 15,438 women aged 35–65 years was used to derive a risk score predicting incident type 2 diabetes. Multivariate Cox regression model coefficients were used to weigh each variable in the calculation of the score. Data from the EPIC-Heidelberg, the Tübingen Family Study for Type 2 Diabetes (TÜF), and the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study were used to validate this score. RESULTS—Information on age, waist circumference, height, history of hypertension, physical activity, smoking, and consumption of red meat, whole-grain bread, coffee, and alcohol formed the German Diabetes Risk Score (mean 446 points [range 118–983]). The probability of developing diabetes within 5 years in the EPIC-Potsdam study increased from 0.3% for 300 to 23.2% for 750 score points. The area under the receiver-operator characteristic (ROC) curve was 0.84 in the EPIC-Potsdam and 0.82 in the EPIC-Heidelberg studies. Correlation coefficients between the German Diabetes Risk Score and insulin sensitivity in nondiabetic individuals were −0.56 in the TÜF and −0.45 in the MeSyBePo studies. ROC values for undiagnosed diabetes were 0.83 in the TÜF and 0.75 in the MeSyBePo studies. CONCLUSIONS—The German Diabetes Risk Score (available at www.dife.de) is an accurate tool to identify individuals at high risk for or with undiagnosed type 2 diabetes.

The metallo-β-lactamase VIM-31 differs from VIM-2 by only two Tyr224His and His252Arg substitutions. Located close to the active site, the Tyr224His substitution is also present in VIM-1, VIM-4, VIM-7 and VIM-12. The VIM-31 variant was reported in 2012 from Enterobacter cloacae and kinetically characterized. It exhibits globally lower catalytic efficiencies than VIM-2. In the present study, we report the three-dimensional structures of VIM-31 in its native (reduced) and oxidized forms. The so-called 'flapping-loop' (loop 1) and loop 3 of VIM-31 were not positioned as in VIM-2 but instead were closer to the active site as in VIM-4, resulting in a narrower active site in VIM-31. Also, the presence of His224 in VIM-31 disrupts hydrogen-bonding networks close to the active site. Moreover, a third zinc-binding site, which also exists in VIM-2 structures, could be identified as a structural explanation for the decreased activity of VIM-MBLs at high zinc concentrations.

Aims/hypothesis The aim of this study was to prospectively examine the association between body iron stores and risk of type 2 diabetes. Methods We designed a case–cohort study among 27,548 individuals within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study. During 7 years of follow-up, 849 incident cases of type 2 diabetes were identified. Of these, 607 remained for analyses after exclusion of participants with missing data or abnormal glucose levels at baseline. A sub-cohort of 2,500 individuals was randomly selected from the full cohort, comprising 1,969 individuals after applying the same exclusion criteria. Results After adjustment for age, sex, BMI, waist circumference, sports activity, bicycling, education, occupational activity, smoking habit, alcohol consumption and circulating levels of γ-glutamyltransferase, alanine aminotransferase, fetuin-A, high-sensitivity C-reactive protein, adiponectin, HDL-cholesterol and triacylglycerol, higher serum ferritin concentrations were associated with a higher risk of type 2 diabetes (RR in the highest vs lowest quintile, 1.73; 95% CI 1.15, 2.61; ptrend00.002). No significant association was observed for soluble transferrin receptor (RR 1.33; 95% CI 0.85, 2.09; ptrend00.50). The soluble transferrin receptor-toferritin ratio was significantly inversely related to risk (RR 0.61; 95% CI 0.41, 0.91; ptrend00.02). Conclusions/interpretation High ferritinlevelsare associated with higher risk of type 2 diabetes independently of established diabetes risk factors and a range of diabetes biomarkers whereas soluble transferrin receptor concentrations are not related torisk. These results support the hypothesisthathigher iron stores below the level of haemochromatosis are associated with risk of type 2 diabetes.

Objective: Hyperandrogenism is a central feature of the polycystic ovary syndrome (PCOS) and might worsen insulin resistance (IR) often seen in PCOS. Androgens act through the androgen receptor (AR). A polymorphic CAG repeat sequence within the AR gene was reported to modulate its transactivation activity. Therefore, we investigated a putative interaction between testosterone and the CAG repeat length polymorphism with respect to IR. Design: In 63 PCOS women with normal glucose tolerance free testosterone, the biallelic CAG repeat length and a multiplicative interaction term were investigated by multiple linear regression analysis for an association with IR as indicated by the homeostasis model assessment of IR (HOMA-IR). Results: Free testosterone was correlated with HOMA-IR. The impact of testosterone on HOMA-IR was modified by the AR CAG length as indicated by an interaction term. This interaction remained significant after adjustment for smoking, age and body mass index. While there was a positive association of free testosterone with HOMA-IR, the interaction term was inversely associated. The model, which explained 42.5% of the variation of HOMA-IR predicted that in carriers of short CAG lengths, an increase in testosterone increased IR. This effect attenuated with rising biallelic CAG length until it turns into the opposite at a CAG length longer than 23. The results were confirmed by using CIGMA as another measure of IR. Conclusions: The association between testosterone and IR is modified by the CAG repeat polymorphism within the AR. Therefore, the evaluation of testosterone effects on IR seems to require consideration of the AR CAG repeat polymorphism in PCOS women.

Disease can be caused by different mechanisms. A possible causal model proposed by Rothman is a complete causal mechanism or a so-called "sufficient cause" consisting of a set of component causes that can be illustrated in a pie chart. However, this model does not allow finding out what sufficient causes produce the majority of cases. The authors' objective was to extend Rothman's work by quantifying the proportion of disease that can be attributed to a class of sufficient causes. The underlying idea was to consider all combinations of a given set of known risk factors and to assign each combination to a class of sufficient causes. This assignment makes it possible to evaluate a class of sufficient causes by the population attributable fraction of the corresponding combination of risk factors. The approach presented was applied to sufficient causes of myocardial infarction by use of data on participants recruited between 1994 and 1998 into the European Prospective Investigation into Cancer and Nutrition-Potsdam Study. As a result, 51.8% of cases were attributed to only four different classes of sufficient causes. In conclusion, the statistical method described in the paper may be beneficial for quantifying the importance of different sufficient causes and for improving the efficiency of public health programs.

Background Inflammation is considered a key mechanism leading to type 2 diabetes, but dietary exposures that lead to inflammation and diabetes are largely unknown.

The aim of the study was to identify a dietary pattern predictive of subsequent annual weight change by using dietary composition information. Study subjects were 24,958 middle-aged men and women of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. To derive dietary patterns, we used the reduced rank regression method with 3 response variables presumed to affect weight change: fat density, carbohydrate density, and fiber density. Annual weight change was computed by fitting a linear regression line to each person's body weight data (baseline, and 2- and 4-y follow-up) and determining the slope. In linear regression models, the pattern score was related to annual weight change. We identified a food pattern of high consumption of whole-grain bread, fruits, fruit juices, grain flakes/cereals, and raw vegetables, and of low consumption of processed meat, butter, high-fat cheese, margarine, and meat to be predictive of subsequent weight change. Mean annual weight gain gradually decreased with increasing pattern score (P for trend < 0.0001), i.e., subjects scoring high for the pattern maintained their weight or gained significantly less weight over time compared with subjects with an opposite pattern. However, the prediction of annual weight change by the food pattern was significant only in nonobese subjects. In this study population, we identified a food pattern characterized by high-fiber and low-fat food choices that can help to maintain body weight or at least prevent excess body weight gain.

Uteroglobin (UG) is a conserved protein which is induced by progesterone and secreted by the epithelia of various mammalian reproductive and respiratory organs. Recombinant bovine uteroglobin (recbUG), consisting of 80 amino acids with a C-terminal His6 tag, was overexpressed in Escherichia coli and purified. The protein was crystallized in two geometric forms, rhomboid and cuneate (wedge-shaped), by the hanging-drop vapour-diffusion method at 295 K. The rhomboid crystals diffracted to a maximum resolution of 1.6 A using synchrotron radiation. These crystals belong to space group P2(1)2(1)2, with unit-cell parameters a = 81.42, b = 82.82, c = 45.26 A, and contain four monomers per asymmetric unit. The cuneate crystals diffracted to 2.35 A resolution using a rotating-anode generator. These crystals belong to space group C222(1), with unit-cell parameters a = 43.39, b = 93.94, c = 77.30 A, and contain two molecules per asymmetric unit.

Increased levels of IL-6 add further risk to the impact of obesity in respect to the development of type 2 diabetes mellitus (T2DM). A C-174G polymorphism within the IL-6 promoter region was shown to influence transcription rate of IL-6. We made use of a nested case-control study within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort of 27,548 individuals, selecting 188 T2DM cases and 376 controls to investigate this polymorphism in respect to development of T2DM. This polymorphism was found to modify the correlation between body mass index (BMI) and IL-6 by showing a much stronger increase of IL-6 at increased BMI for CC genotypes compared with GG genotypes. Interestingly, C-174G polymorphism was found to be an effect modifier for the impact of BMI regarding T2DM. Whereas BMI greater than or equal to 28 kg/m2 increased the risk of T2DM 3.44-fold [95% confidence interval (CI), 1.34- to 8.24-fold] for GG genotypes and 2.94-fold (95% CI, 1.56- to 5.56-fold) for GC genotypes, we found a 17.68-fold (95% CI, 3.57- to 87.66-fold) increase in risk for CC genotypes. In conclusion, obese individuals with BMI greater than or equal to 28 kg/m2 carrying the CC genotype showed a more than 5-fold increased risk of developing T2DM compared with the remaining genotypes and, hence, might profit most from weight reduction.

Analysis of dietary patterns is considered a useful approach to the examination of diet-disease associations. This study examined the risk of incident hypertension associated with dietary patterns in 8,552 women in the EPIC (European Prospective Investigation into Cancer and Nutrition)-Potsdam Study. The baseline examination was carried out between 1994 and 1998. During 2-4 years of follow-up (through May 15, 2002), 123 incident hypertension cases were verified by medical records. Two exploratory dietary patterns, a "traditional cooking" pattern (meat, cooked vegetables, sauce, potatoes, and poultry) and a "fruits and vegetables" pattern (fruits, raw vegetables, and vegetable oil), were identified by exploratory factor analysis and confirmed by confirmatory factor analysis. Additionally, a hypothesis-oriented pattern based on the Dietary Approaches to Stop Hypertension (DASH) Study was defined (fruits, vegetables, and milk products). Patterns' associations with disease risk were estimated by Cox regression. While no significant associations were observed for the traditional cooking pattern or the fruits and vegetables pattern after adjustment for potential confounders, women in the third quartile of the DASH pattern were at lower risk than women in the lowest quartile (hazard rate ratio = 0.51, 95% confidence interval: 0.29, 0.89). These results suggest that this hypothesis-oriented pattern might play an important role in the risk of hypertension.

Purpose: To compare history of 22 different diseases reported during an in-person interview with that reported on a mailed self-administered questionnaire. Methods: 7841 participants of the European Prospective Investigation into Cancer (EPIC)-Potsdam study. The interview at baseline and the questionnaire at follow-up approximately 2 years later included identical questions about whether the participant had ever had a physician diagnosis of each disease. Incident diagnoses occurring in the interval between the interview and questionnaire were excluded from the analysis. Results: Agreement between self-report from the interview and from the questionnaire was highest (κ=0.83–0.88) for myocardial infarction, cancer and diabetes mellitus; it was lower (κ=0.68–0.77) for gout, hypertension, hay fever, asthma, osteoporosis, ulcer of the duodenum, thyroid disease, stroke, and kidney stones, and was lowest (κ=0.39–0.59) for chronic gastritis, ulcer of the stomach, cerebral ischemia, benign tumor, inflammatory bowel disease, angina pectoris, hyperlipidemia, rheumatism, colon polyps and skin disease. The poor agreement for less severe or more transient diseases was primarily a result of disease frequently being reported at the interview but not on the questionnaire. Conclusion: Self-administered questionnaires do not generate same information particularly for less severe or transient diseases as personal interviews. For these diseases, self-administered questionnaires are not recommended. Pilot studies that test validity will be necessary.

A subclinical inflammatory reaction has been shown to precede the onset of type 2 (non-insulin-dependent) diabetes. We therefore examined prospectively the effects of the central inflammatory cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha (TNF-alpha) on the development of type 2 diabetes. We designed a nested case-control study within the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study including 27,548 individuals. Case subjects were defined to be those who were free of type 2 diabetes at baseline and subsequently developed type 2 diabetes during a 2.3-year follow-up period. A total of 192 cases of incident type 2 diabetes were identified and matched with 384 non-disease-developing control subjects. IL-6 and TNF-alpha levels were found to be elevated in participants with incident type 2 diabetes, whereas IL-1beta plasma levels did not differ between the groups. Analysis of single cytokines revealed IL-6 as an independent predictor of type 2 diabetes after adjustment for age, sex, BMI, waist-to-hip ratio (WHR), sports, smoking status, educational attainment, alcohol consumption, and HbA(1c) (4th vs. the 1st quartile: odds ratio [OR] 2.6, 95% CI 1.2-5.5). The association between TNF-alpha and future type 2 diabetes was no longer significant after adjustment for BMI or WHR. Interestingly, combined analysis of the cytokines revealed a significant interaction between IL-1beta and IL-6. In the fully adjusted model, participants with detectable levels of IL-1beta and elevated levels of IL-6 had an independently increased risk to develop type 2 diabetes (3.3, 1.7-6.8), whereas individuals with increased concentrations of IL-6 but undetectable levels of IL-1beta had no significantly increased risk, both compared with the low-level reference group. These results were confirmed in an analysis including only individuals with HbA(1c)

Nucleic acids research 43(20), 9680-9693 (2015). doi:10.1093/nar/gkv1056, Published by Information Retrieval Ltd., London

Objective: To evaluate the influence of recent weight changes (weight gain, loss and cycling) on subsequent weight changes. Design: Prospective cohort study with 2 y of follow-up. Data analysis with a polytomous logistic regression model. Subjects: A total of 18 001 non-smoking subjects, 6689 men and 11 312 women, from the general population. Measurements: Body height and weight measurements and interview data on lifestyle habits and medical history at baseline. For follow-up, self-administered questionnaires for assessment of body weight and incident diseases. Results: Recent changes in body weight, that is weight gain, weight loss and weight cycling, were significant predictors of subsequent weight changes in both men and women after controlling for age, baseline BMI and several lifestyle and behavioural characteristics as potential confounding factors. Weight cycling before baseline was the strongest predictor of subsequent large weight gain (≥2 kg) with an odds ratio (OR) of 4.84 (95% confidence interval (CI) 3.34–7.02) in men. In women, prior weight loss was the strongest predictor of subsequent large weight gain (OR 4.77; 95% CI 3.63–6.03), followed by weight cycling (OR 3.02; 95% CI 2.15–4.25). Conclusion: These data indicate the need for thorough weight history assessment to identify those who are most likely to gain weight. Effective weight control before the development of obesity or after intentional weight loss due to obesity should be a primary goal in the management of obesity.

Oven aging was applied for about 8800 hours (more than one year) to evaluate the long-term thermal stability of post-used HDPE material recycled from bottle crates. For recycling, the remelting-restabilization technique was applied. To study the effect of restabilization, crystallinity and melt flow rate were monitored during heat aging. Furthermore, tensile strength and tensile impact strength were followed together with the time until embrittlement. These data were enriched with microphotographs of the specimens' surfaces. Finally, repigmentation was used to evaluate the role of new pigments on the final performance of the recycled material. The results illustrate that restabilization is mandatory for improving the long-term thermal stability of the post-used crate material, enabling its reuse in the original application.

Various cross-sectional studies suggest that a polymorphism (E23K) within the ATP-sensitive K+ channel KCNJ11 gene is associated with type 2 diabetes (1). However, only two prospective studies have addressed the relation between KCNJ11 E23K and type 2 diabetes, and these studies were intervention trials based on individuals with impaired fasting glucose and impaired glucose tolerance (2–4). With respect to functional effects, recent studies have been inconsistent regarding demonstration of a relation of the polymorphism with markers of insulin secretion (3,5,6), although in vitro studies clearly suggested a defect in insulin secretion (7–9). One study proposed a relation to glucagon response, while insulin secretion itself was not affected (10). However, the relation between polymorphism and insulin secretion might have been masked in some of those studies by differences of insulin sensitivity, and detailed analysis might thus require consideration of insulin sensitivity of the study participants, such as that given in the disposition index (11). We investigated the effect of KCNJ11 E23K on diabetes risk within a prospective case-cohort study ( n = 2,945) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. We additionally tested the association with diabetes in a second independent cross-sectional study, the Metabolic Syndrome Berlin Potsdam (MeSyBePo) cohort, from the same geographical region ( n = 1,891). Within this second study, the association between polymorphism and disposition index was additionally investigated. We designed a case-cohort study within the EPIC-Potsdam study, a prospective cohort involving 27,548 Caucasian volunteers, mainly aged 35–65 years, from the general population (12–14). A total of 2,263 individuals were randomly selected for a subcohort. Because the …

BMC systems biology 8(1), 55 (2014). doi:10.1186/1752-0509-8-55, Published by BioMed Central, London

BACKGROUND Renoprotective actions of angiotensin receptor blockers are not well established in normotensive, low-grade proteinuric glomerular diseases. We examined the effect of low-dose telmisartan (LT) and high-dose telmisartan (HT) versus conventional antihypertensive therapy in the rat anti-Thy1.1 model of glomerulonephritis. METHODS Rats were randomized on Day 4 after disease induction to no treatment (CT, control), LT or HT or hydrochlorothiazide + hydralazine (HCT + H). RESULTS All rats remained normotensive: HT and HCT + H reduced blood pressure by 15-20%. LT, HT and HCT + H reduced glomerular endothelial cell proliferation and glomerular and interstitial matrix deposition on Day 14. Only HT reduced podocyte damage and tubular cell dedifferentiation on Day 9 and mesangial cell activation on Day 14. By gene expression analysis arrays, we identified discs-large homolog 1 and angiopoietin-like 4 as potential mediators of the HT effects. In addition, we identified several pathways possibly related to the pleiotropic effects of HT, including growth factor signalling, mammalian target of rapamycin signalling, protein ubiquitination, the Wnt-beta catenin pathway and hypoxia signaling. CONCLUSIONS In summary, treatment with HT, initiated after the induction of disease, ameliorates glomerular and tubulointerstitial damage. We provide the first comprehensive insight into the mechanisms underlying the renoprotective effect of high-dose angiotensin II receptor blockers (ARBs). Our study lays the basis for future investigations on novel pathways affected by ARBs in renal disease.

Bacteria can defend themselves against β-lactam antibiotics through the expression of class B β-lactamases, which cleave the β-lactam amide bond and render the molecule harmless. There are three subclasses of class B β-lactamases (B1, B2, and B3), all of which require Zn 2+ for activity and can bind either one or two zinc ions. Whereas the B1 and B3 metallo-β-lactamases are most active as dizinc enzymes, subclass B2 enzymes, such as Aeromonas hydrophila CphA, are inhibited by the binding of a second zinc ion. We crystallized A. hydrophila CphA in order to determine the binding site of the inhibitory zinc ion. X-ray data from zinc-saturated crystals allowed us to solve the crystal structures of the dizinc forms of the wild-type enzyme and N220G mutant. The first zinc ion binds in the cysteine site, as previously determined for the monozinc form of the enzyme. The second zinc ion occupies a slightly modified histidine site, where the conserved His118 and His196 residues act as metal ligands. This atypical coordination sphere probably explains the rather high dissociation constant for the second zinc ion compared to those observed with enzymes of subclasses B1 and B3. Inhibition by the second zinc ion results from immobilization of the catalytically important His118 and His196 residues, as well as the folding of the Gly232-Asn233 loop into a position that covers the active site.

An incidence rate ratio (IRR) is a meaningful effect measure in epidemiology if it is adjusted for all important confounders. For evaluation of the impact of adjustment, adjusted IRRs should be compared with crude IRRs. The aim of this methodological study was to present a statistical approach for testing the equality of adjusted and crude IRRs and to derive a confidence interval for the ratio of the two IRRs. The method can be extended to compare two differently adjusted IRRs and, thus, to evaluate the effect of additional adjustment. The method runs immediately on existing software. To illustrate the application of this approach, the authors studied adjusted IRRs for two risk factors of type 2 diabetes using data from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study from 2005. The statistical method described may be helpful as an additional tool for analyzing epidemiologic cohort data and for interpreting results obtained from Cox regression models with adjustment for different covariates.

It remains unclear what long-term effects of substituting carbohydrates at the expense of protein or fat may have with regard to diabetes risk. Our objective was to evaluate carbohydrate intake in predicting type 2 diabetes using substitution models for fat and protein. We conducted a prospective cohort study of 9702 men and 15 365 women aged 35–65 years and free of diabetes at baseline (1994–8) who were followed for incident type 2 diabetes until 2005. Dietary intake of macronutrients was estimated with a validated FFQ. We estimated the relative risk (RR) using Cox proportional hazards analysis. During 176 117 person-years of follow-up we observed 844 incident cases of physician-confirmed type 2 diabetes. After adjustment for age, BMI, waist circumference, potential lifestyle and dietary confounders, substituting 5 % of energy intake from total, saturated, or monounsaturated fat with carbohydrates was not associated with diabetes risk. In contrast, substituting carbohydrates for protein or PUFA was inversely related to diabetes risk (RR for 5 % energy substitution of protein 0·77 (95 % CI 0·64, 0·91); RR for PUFA 0·83 (95 % CI 0·70, 0·98)). These associations appeared to be similar for men and women, but gained statistical significance only among men for protein (RR 0·78 (95 % CI 0·61, 0·99)). Restricted cubic spline regression did not indicate non-linearity of these associations (P for non-linearity in full cohort was 0·353 and 0·349). In conclusion, a higher carbohydrate intake at the expense of protein and PUFA might be associated with decreased diabetes risk.

Recently, a food pattern predictive for prospective weight change was identified within the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort. Given the possible impact of weight change on cardiovascular disease (CVD) risk, we examined the association between the above mentioned food pattern and risk of CVD. The analyzed food pattern was defined by a high consumption of whole-grain bread, fruits, fruit juices, grain flakes and/or cereals, and raw vegetables, and a low consumption of processed meat, butter, high-fat cheese, margarine, and meat other than poultry. The associations between quartiles of the food pattern score and CVD morbidity and mortality were examined in 26,238 subjects of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort using a Cox's Proportional Hazards model for competing risks. During 6.4 y of follow-up, 379 incident cases of CVD were identified, of which 68 were fatal events. The food pattern was not associated with risk of nonfatal CVD. After adjusting for cardiovascular risk factors, the hazard ratios for fatal CVD across increasing quartiles of the score were 1.00, 0.85, 0.31, and 0.47, respectively (P for trend = 0.016). The association of the food pattern with CVD risk differed between fatal and nonfatal events (P for difference = 0.05). These findings from a large German cohort indicate that a food pattern predicting prospective weight change may be associated with the risk of fatal CVD.

C-reactive protein (CRP) was proposed as a stronger predictor of cardiovascular events than low-density lipoprotein cholesterol (LDL-C); however, these associations may differ between myocardial infarction (MI) and stroke. We compared statistically the associations of CRP and LDL-C levels with risk of MI versus stroke and examined to what extent consideration of CRP or LDL-C increases the population attributable fractions (PAFs) of MI and stroke beyond traditional risk factors among 27,548 subjects from the European Prospective Investigation into Cancer and Nutrition-Potsdam Study in a case-cohort design. Among subjects without prior MI or stroke, 156 developed MI and 132 stroke during 6.0 years of follow-up. In adjusted competing risk analyses CRP was positively related to MI and stroke (P difference between endpoints = 0.55), whereas LDL-C was related to MI but not stroke (P difference between endpoints = 0.003). The PAF for smoking, diabetes, and hypertension combined was 0.76 for MI, and 0.58 for stroke. With additional consideration of CRP the PAFs were 0.80 and 0.68, while with addition of LDL-C the PAFs were 0.88 and 0.55. We conclude that CRP is equally strongly related to risk of MI and stroke, whereas LDL-C is related to risk of MI but not stroke. Consideration of LDL-C beyond smoking, diabetes and hypertension may increase the PAF of MI slightly more than CRP. In contrast, consideration of CRP but not of LDL-C may increase the PAF of stroke beyond these factors.

ObjectiveTo investigate the association of a posteriori dietary patterns with overall survival of older Europeans.Design and settingThis is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort). Analyses controlled for all known potential risk factors.SubjectsIn total, 74 607 men and women, 60 years or older at enrolment and without previous coronary heart disease, stroke or cancer, with complete information about dietary intakes and potentially confounding variables, and with known survival status as of December 2003, were included in the analysis.ResultsAn increase in the score which measures the adherence to the plant-based diet was associated with a lower overall mortality, a one standard deviation increment corresponding to a statistically significant reduction of 14% (95% confidence interval 5–23%). In country-specific analyses the apparent association was stronger in Greece, Spain, Denmark and The Netherlands, and absent in the UK and Germany.ConclusionsGreater adherence to the plant-based diet that was defined a posteriori in this population of European elders is associated with lower all-cause mortality. This dietary score is moderately positively correlated with the Modified Mediterranean Diet Score that has been constructed a priori and was also shown to be beneficial for the survival of the same EPIC-Elderly cohort.

Obesity is a well-established risk factor for type 2 diabetes (1–3). However, while several studies (4–10) suggest that anthropometric measurements that describe central fat distribution are superior in predicting type 2 diabetes compared with measurements of general adiposity, this issue remains controversial (11–14). The aim of this study was to compare different anthropometric measurements and derived estimates of body composition, in particular BMI, waist-to-height ratio, waist-to-hip ratio (WHR), metric index, and percentage body fat, in their ability to predict risk of type 2 diabetes in a large prospective cohort study of men and women. The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study includes 27,548 subjects, 16,644 women aged mainly 35–65 years and 10,904 men aged mainly 40–65 years, from the general population of Potsdam, Germany, recruited between 1994 and 1998 (15). The baseline examination included anthropometric measurements (16,17) as well as a personal interview and a questionnaire on prevalent diseases and sociodemographic and lifestyle characteristics. Follow-up questionnaires have been administered every 2–3 years. Response rates for follow-up rounds 1, 2, 3, and 4 were 96, 95, 91, and 90% (31 August 2005), respectively. All potential incident cases of diabetes were verified by the diagnosing physician using …

Dietary pattern analysis, which reflects the complexity of dietary intake, has received considerable attention by nutritional epidemiology. For a long time, two general approaches have been used to define these summary variables in observational studies. The exploratory approach is based only on the data of the study, whereas the hypothesis-oriented approach constructs pattern variables based on scientific evidence available before the study. Recently, a new statistical method, reduced rank regression, was applied to nutritional epidemiology that is exploratory by nature, but can use scientific evidence by focusing on disease-related dietary components or biomarkers. Several studies, both observational and clinical, suggest that dietary patterns may predict the risk of CHD and stroke. In the present review, we describe the results of these studies and the available evidence regarding the relationships between dietary patterns and risk of CVD and we discuss limitations and strengths of the statistical methods used toextract dietary patterns.

Homozygosity for the interleukin-6 (IL-6) g.-174GC promoter polymorphism has recently been associated with indices of overweight. Homozygous subjects were observed to have reduced energy expenditure, suggesting that lower IL-6 gene transcription, caused by the IL-6 g.-174GC promoter polymorphism, may be associated with obesity. The aim of this study was to investigate the association of this polymorphism with long-term weight gain. For 334 normal weight (20BMIor = 25 kg/m2) and 334 obese (BMI30 kg/m2) subjects matched by age and sex originating from the population-based EPIC-Potsdam Study, recalled weight change from age 25 to study enrollment was determined, the IL-6 g.-174GC promoter polymorphism was defined, and plasma concentrations of IL-6 and C-reactive protein were measured. The IL-6 g.-174GC promoter polymorphism was significantly associated with obesity (chi2 = 7,34, p = 0.026). Odds ratios for subjects with GC and CC genotypes for obesity were 1.19 (95% CI: 0.84 to 1.68; p = 0.323) and 1.91 (95% CI: 1.19 to 3.08; p = 0.007), respectively. Recalled weight change from age 25 years to study enrollment differed significantly according to genotype (p = 0.044) and was most pronounced in subjects with the CC genotype, suggesting that the IL-6 g.-174GC promoter polymorphism is a susceptibility or modifying locus for common obesity and weight gain.

Contains fulltext : 49468.pdf (Publisher’s version ) (Closed access) Epidemiologic studies suggest that a high intake of fruits and vegetables is associated with decreased risk of cancers of the upper aero-digestive tract. We studied data from 345,904 subjects of the prospective European Investigation into Cancer and Nutrition (EPIC) recruited in seven European countries, who had completed a dietary questionnaire in 1992-1998. During 2,182,560 person years of observation 352 histologically verified incident squamous cell cancer (SCC) cases (255 males; 97 females) of the oral cavity, pharynx, larynx, and esophagus were identified. Linear and restricted cubic spline Cox regressions were fitted on variables of intake of fruits and vegetables and adjusted for potential confounders. We observed a significant inverse association with combined total fruits and vegetables intake (estimated relative risk (RR) = 0.91; 95% confidence interval (95% CI) 0.83-1.00 per 80 g/d of consumption), and nearly significant inverse associations in separate analyses with total fruits and total vegetables intake (RR: 0.97 (95% CI: 0.92-1.02) and RR = 0.89 (95% CI: 0.78-1.02) per 40 g/d of consumption). Overall, vegetable subgroups were not related to risk with the exception of intake of root vegetables in men. Restricted cubic spline regression did not improve the linear model fits except for total fruits and vegetables and total fruits with a significant decrease in risk at low intake levels (

Dietary patterns are comprehensive variables of dietary intake appropriate to model the complex exposure in nutritional research. The objectives of this study were to identify dietary patterns by applying two statistical methods, principal component analysis (PCA) and reduced rank regression (RRR), and to assess their ability to predict all-cause mortality. Motivated by previous studies we chose percentages of energy from different macronutrients as response variables in the RRR analysis. We used data from 9356 German elderly subject enrolled in the European Prospective Investigation into Cancer and Nutrition study. The first RRR pattern, subjects which explained 30·8 % of variation in energy sources and especially much variation in intake of saturated fat, monounsaturated fat and carbohydrates was a significant predictor of all-cause mortality. The pattern score had high positive loadings in all types of meat, butter, sauces and eggs, and was inversely associated with bread and fruits. After adjustment for other known risk factors, the relative risks from the lowest to highest quintiles of the first RRR pattern score were 1·0, 1·01, 0·96, 1·32, 1·61 (P for trend: 0·0004). In contrast, the first two PCA patterns explaining 19·7 % of food intake variation but only 7·0 % of variation in energy sources were not related to mortality. These results suggest that variation in macronutrients is meaningful for mortality and that the RRR method is more appropriate than the classic PCA method to identify dietary patterns relevant to mortality.

We examined prospectively the association between weight change during adulthood and breast cancer risk, using data on 1358 incident cases that developed during 5.8 years of follow-up among 40,429 premenopausal and 57,923 postmenopausal women from six European countries, taking part in the European prospective investigation into cancer and nutrition study. Multivariate Cox regression models were used to calculate hazard ratios according to weight change (kg), defined as the weight difference between age at enrollment and age 20 adjusted for other risk factors. Changes in weight were not associated with premenopausal breast cancer risk. In postmenopausal women, weight gain was positively associated with breast cancer risk only among noncurrent hormone replacement therapy (HRT) users (P-trend < or = 0.0002). Compared to women with a stable weight (+/-2 kg), the relative risk for women who gained 15-20 kg was 1.50 (95% confidence interval (CI) 1.06-2.13). The pooled RR per weight gain increment of 5 kg was 1.08 (95% CI 1.04-1.12). Weight gain was not associated with breast cancer risk in current HRT users, although, overall, these women experienced a much higher risk of breast cancer compared with nonusers. Our findings suggest that large adult weight gain was a significant predictor of breast cancer in postmenopausal women not taking exogenous hormones.

Objective: The association between consumption of fruit and vegetables and risk of ovarian cancer is still unclear from a prospective point of view. Methods: Female participants (n = 325,640) of the European Prospective Investigation into Cancer and Nutrition study, free of any cancer at baseline, were followed on average for 6.3 years to develop ovarian cancer. During 2,049,346 person-years, 581 verified cases of primary, invasive epithelial ovarian cancer were accrued. Consumption of fruits and vegetables as well as subgroups of vegetables, estimated from validated dietary questionnaires and calibrated thereafter, was related to ovarian cancer incidence in multivariable hazard regression models. Histologic subtype specific analyses were done. Results: Total intake of fruit and vegetables, separately or combined, as well as subgroups of vegetables (fruiting, root, leafy vegetables, cabbages) was unrelated to risk of ovarian cancer. A high intake of garlic/onion vegetables was associated with a borderline significant reduced risk of this cancer. The examination by histologic subtype indicated some differential effects of fruit and vegetable intake on ovarian cancer risk. Conclusion: Overall, a high intake of fruits and vegetables did not seem to protect from ovarian cancer. Garlic/onion vegetables may exert a beneficial effect. The study of the histologic subtype of the tumor warrants further investigation.

Overall dietary patterns have been associated with health and longevity. We used principal component (PC) and cluster analyses to identify the prevailing dietary patterns of 99 744 participants, aged 60 years or older, living in nine European countries and participating in the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort) and to examine their socio-demographic and lifestyle correlates. Two PC were identified: PC1 reflects a 'vegetable-based' diet with an emphasis on foods of plant origin, rice, pasta and other grain rather than on margarine, potatoes and non-alcoholic beverages. PC2 indicates a 'sweet- and fat-dominated' diet with a preference for sweets, added fat and dairy products but not meat, alcohol, bread and eggs. PC1 was associated with a younger age, a higher level of education, physical activity, a higher BMI, a lower waist:hip ratio and never and past smoking. PC2 was associated with older age, less education, never having smoked, a lower BMI and waist:hip ratio and lower levels of physical activity. Elderly individuals in southern Europe scored positively on PC1 and about zero on PC2, whereas the elderly in northern Europe scored negatively on PC1 and variably on PC2. The results of cluster analysis were compatible with the indicated dietary patterns. 'Vegetable-based' and a 'sweet- and fat-dominated' diets are prevalent among the elderly across Europe, and there is a north - south gradient regarding their dietary choices. Our study contributes to the identification of groups of elderly who are likely to have different prospects for long-term disease occurrence and survival. © The Authors 2005.

Objective To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. Design Multicentre, prospective cohort study. Setting Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom). Participants 74 607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables. Main outcome measures Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression. Results An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%). Conclusion The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.